Pyridine → HCID 178474446, compound

HRID 1747200Notes

Reaction equation

HRID 1747200 reaction equation
ClC([O:4][CH2:5]C(CC)CCCC)=O.[C:13]([NH:16][C:17]1[S:18][C:19]([C:23]2[N:24]=[C:25]([NH:28][C:29]3[CH:30]=[C:31]([C:35](=[N:37][OH:38])O)[CH:32]=[CH:33][CH:34]=3)[S:26][CH:27]=2)=[C:20]([CH3:22])[N:21]=1)(=[O:15])[CH3:14].[N:39]1C=CC=CC=1>CN(C=O)C.O>[OH:4][C:5]1[O:38][N:37]=[C:35]([C:31]2[CH:30]=[C:29]([NH:28][C:25]3[S:26][CH:27]=[C:23]([C:19]4[S:18][C:17]([NH:16][C:13](=[O:15])[CH3:14])=[N:21][C:20]=4[CH3:22])[N:24]=3)[CH:34]=[CH:33][CH:32]=2)[N:39]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 627832-Ethylhexyl chloroformateHCID 178474447HCID 178474447, compound

Product 1

HCID 178474446HCID 178474446, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

2-Ethylhexyl chloroformate (101.22 μl; 0.51 mmol; 1.00 eq.) is added dropwise to an ice cooling mixture of 3-{[2′-(acetylamino)-4′-methyl-4,5′-bi-1,3-thiazol-2-yl]amino}-N-hydroxybenzenecarboximidic acid (60) obtained as described above in Example 60 (200.00 mg; 0.51 mmol; 1.00 eq.) and anhydrous pyridine (41.56 μl; 0.51 mmol; 1.00 eq.) in DMF (2.00 ml). The resulting mixture is stirred at 0° C. for 30 min. It is diluted with water and extracted with EtOAc (3 times). The extracts are washed with water and dried over Na2SO4. Solvents are evaporated and the resulting crude intermediate is suspended 1 to in xylene (2 mL) and heated at 150° C. for 2 hours. The solvents are evaporated and the resulting crude product is purified by flash chromatography, affording N-(2-{[3-(5-hydroxy-1,2,4-oxadiazol-3-yl)phenyl]amino}-4′-methyl-4,5′-bi-1,3-thiazol-2′-yl)acetamide (61) as parent (134.90 mg; 64.70%). A sample (88.00 mg; 0.21 mmol; 1.00 eq.) is suspended in water (2.50 ml) and THF (2.50 ml) and potassium hydroxide solution (416.15 μl; 0.50 M; 0.21 mmol; 0.98 eq.) is added. The resulting solution is filtered through cotton and freeze-dried, affording (61) as brown powder (82.8 mg; 91.58%). 1H NMR (DMSO-d6, 300 MHz) δ 2.12 (s, 3H), 2.52 (s, 3H, COCH3), 6.88 (s, 1H), 7.34 (m, 2H), 7.84 (m, 2H), 10.34 (s, 1H). M− (ESI): 413; M+ (ESI): 415. HPLC, Rt: 3.09 min (purity: 97.6%).

Workup

  1. customobtained
  2. extractionextracted with EtOAc (3 times)
  3. washThe extracts are washed with water
  4. dry with materialdried over Na2SO4
  5. customSolvents are evaporated
  6. temperatureheated at 150° C. for 2 hours
  7. customThe solvents are evaporated
  8. customthe resulting crude product is purified by flash chromatography

Sources & evidence

ORD record
ord-bcdc967145bd459ca81200c95fa5e82e
Source dataset
uspto-grants-2015_10
Patent number
US09150561B2

Reaction notes

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